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No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis.
Loley, Christina; Alver, Maris; Assimes, Themistocles L; Bjonnes, Andrew; Goel, Anuj; Gustafsson, Stefan; Hernesniemi, Jussi; Hopewell, Jemma C; Kanoni, Stavroula; Kleber, Marcus E; Lau, King Wai; Lu, Yingchang; Lyytikäinen, Leo-Pekka; Nelson, Christopher P; Nikpay, Majid; Qu, Liming; Salfati, Elias; Scholz, Markus; Tukiainen, Taru; Willenborg, Christina; Won, Hong-Hee; Zeng, Lingyao; Zhang, Weihua; Anand, Sonia S; Beutner, Frank; Bottinger, Erwin P; Clarke, Robert; Dedoussis, George; Do, Ron; Esko, Tõnu; Eskola, Markku; Farrall, Martin; Gauguier, Dominique; Giedraitis, Vilmantas; Granger, Christopher B; Hall, Alistair S; Hamsten, Anders; Hazen, Stanley L; Huang, Jie; Kähönen, Mika; Kyriakou, Theodosios; Laaksonen, Reijo; Lind, Lars; Lindgren, Cecilia; Magnusson, Patrik K E; Marouli, Eirini; Mihailov, Evelin; Morris, Andrew P; Nikus, Kjell; Pedersen, Nancy.
Affiliation
  • Loley C; Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
  • Alver M; DZHK (German Centre for Cardiovascular Research), partner site Hamburg-Lübeck-Kiel, Lübeck, Germany.
  • Assimes TL; Estonian Genome Center, University of Tartu, Tartu, Estonia.
  • Bjonnes A; Institute of Molecular and Cell Biology, Tartu, Estonia.
  • Goel A; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine Stanford, Standford, California, USA.
  • Gustafsson S; Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.
  • Hernesniemi J; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Hopewell JC; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Kanoni S; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
  • Kleber ME; Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
  • Lau KW; Department of Cardiology, Heart Hospital and University of Tampere School of Medicine, Tampere, Finland.
  • Lu Y; CTSU, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Lyytikäinen LP; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Nelson CP; Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Nikpay M; CTSU, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Qu L; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, USA.
  • Salfati E; Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
  • Scholz M; Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere, Finland.
  • Tukiainen T; Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
  • Willenborg C; NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
  • Won HH; Ruddy Canadian Cardiovascular Genetics Centre University of Ottawa Heart Institute, Ottawa, Canada.
  • Zeng L; Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Zhang W; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine Stanford, Standford, California, USA.
  • Anand SS; Institute for Medical Informatics, Statistics and Epidemiology/Medical Faculty/University of Leipzig, Leipzig, Germany.
  • Beutner F; LIFE Research Center of Civilization Diseases, Leipzig, Germany.
  • Bottinger EP; Analytic and Translation Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
  • Clarke R; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
  • Dedoussis G; DZHK (German Centre for Cardiovascular Research), partner site Hamburg-Lübeck-Kiel, Lübeck, Germany.
  • Do R; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Germany and University Heart Center Luebeck, Campus Lübeck, Lübeck, Germany.
  • Esko T; Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Samsung Medical Center, Seoul, Korea.
  • Eskola M; Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
  • Farrall M; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, München, Germany.
  • Gauguier D; Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
  • Giedraitis V; Department of Cardiology, Ealing Hospital National Health Service (NHS) Trust, Middlesex, UK.
  • Granger CB; Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
  • Hall AS; LIFE Research Center of Civilization Diseases, Leipzig, Germany.
  • Hamsten A; Heart Center Leipzig, Cardiology, University of Leipzig, Leipzig, Germany.
  • Hazen SL; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, USA.
  • Huang J; CTSU, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Kähönen M; Harokopio University Athens, Athens, Greece.
  • Kyriakou T; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, USA.
  • Laaksonen R; The Center for Statistical Genetics, Icahn School of Medicine at Mount Sinai, New York, USA.
  • Lind L; The Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, USA.
  • Lindgren C; The Zena and Michael A. Weiner Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, USA.
  • Magnusson PK; Estonian Genome Center, University of Tartu, Tartu, Estonia.
  • Marouli E; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
  • Mihailov E; Department of Cardiology, Heart Hospital and University of Tampere School of Medicine, Tampere, Finland.
  • Morris AP; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Nikus K; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Pedersen N; INSERM, UMRS1138, Centre de Recherche des Cordeliers, Paris, France.
Sci Rep ; 6: 35278, 2016 10 12.
Article in En | MEDLINE | ID: mdl-27731410
In recent years, genome-wide association studies have identified 58 independent risk loci for coronary artery disease (CAD) on the autosome. However, due to the sex-specific data structure of the X chromosome, it has been excluded from most of these analyses. While females have 2 copies of chromosome X, males have only one. Also, one of the female X chromosomes may be inactivated. Therefore, special test statistics and quality control procedures are required. Thus, little is known about the role of X-chromosomal variants in CAD. To fill this gap, we conducted a comprehensive X-chromosome-wide meta-analysis including more than 43,000 CAD cases and 58,000 controls from 35 international study cohorts. For quality control, sex-specific filters were used to adequately take the special structure of X-chromosomal data into account. For single study analyses, several logistic regression models were calculated allowing for inactivation of one female X-chromosome, adjusting for sex and investigating interactions between sex and genetic variants. Then, meta-analyses including all 35 studies were conducted using random effects models. None of the investigated models revealed genome-wide significant associations for any variant. Although we analyzed the largest-to-date sample, currently available methods were not able to detect any associations of X-chromosomal variants with CAD.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Coronary Artery Disease / Chromosomes, Human, X Type of study: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limits: Female / Humans / Male Language: En Journal: Sci Rep Year: 2016 Type: Article Affiliation country: Germany
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Coronary Artery Disease / Chromosomes, Human, X Type of study: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limits: Female / Humans / Male Language: En Journal: Sci Rep Year: 2016 Type: Article Affiliation country: Germany